Based on our preliminary data that immune complex injury of the lung is related to the generation of oxygen metabolites, we will explore in detail the role of the products in lung injury produced by intrapulmonary deposition of immune complexes in rats. We will employ inhibitors of oxygen metabolites (superoxide dismutase, catalase, scavengers of oxygen free radicals), as well as the antioxidant vitamin E and inhibitors of rat liposomal proteases to map the nature of the factors responsible for lung injury. Careful morphological analysis (by light and transmission electron microscopy) will be done on injured and on protected lungs. Biochemical analysis of changes in connective tissue metabolism and synthesis (collagenous and noncollagenous proteins, glycosaminoglycans, collagen types) will be done in acute immune complex induced injury. Bronchioalveolar lavage fluids will be examined from evidence of activators of C3 and/or C5. Also, in vitro approaches will be used to determine if immune complex or chemotactic factor activation of rat neutrophil and alveolar macrophages results in damage or changes in endothelial cells, Type II alveolar cells and lung fibroblasts. We will also pursue our preliminary evidence suggesting that inhibitors of oxygen metabolites reduce in vitro substrate (protein) hydrolysis by activated neutrophils. Finally, we will determine if immune complexes containing secretory IgA are phlogistic in the lung.